Glycated haemoglobin reduction and fixed ratio combinations of analogue basal insulin and glucagon-like peptide-1 receptor agonists: A systematic review

BACKGROUND Fixed ratio combinations（FRCs） of analogue basal insulin and glucagon-like peptide-1 receptor agonists are a newer addition to the therapeutic armamentarium for the management of type 2 diabetes mellitus. They reduce treatment complexity by combining two injectables in a single daily injectable, thus potentially improving adherence and persistence. Clinicians wanting to use FRCs would need to choose between members of the class.AIM To describe and contrast the glycated haemoglobin reduction of two FRCs of analogue basal insulin and glucagon like peptide-1 receptor agonist in adults with type 2 diabetes mellitus.METHODS The following Population, Intervention, Comparison, Outcome question was used for the primary analysis: Among adult patients with type 2 diabetes mellitus [P], what is the effect of i Glar Lixi [I] compared to IDeg Lira [C] for bringing about glycaemic control（as measured by reduction in glycosylated haemoglobin） [O]? The Prisma Statement was used as a guideline for framing this systematic review. We searched Pub Med, EMBASE and Cochrane library databases and Clinicaltrials.gov using various keywords and medical search headings related to type 2 diabetes mellitus, i Glarlixi, IDeg Lira and glycated haemoglobin A1 c.RESULTS All 14 studies identified by the systematic search met the primary efficacy endpoint of reduction in glycated haemoglobin. There were no head-to-head studies between the FRCs of i Glarlixi and IDeg Lira, and we therefore did an indirect comparison based on a common comparator of insulin glargine U100. Both i Glar Lixi and IDeg Lira effectively reduce glycated haemoglobin when compared to insulin glargine U100. However, using indirect comparisons, IDeg Lira had a greater haemoglobin A1 c reducing ability（0.6% vs 0.3%）. The indirect comparison is limited by the differences between the studies; the fasting blood glucose targets were slightly higher for i Glar Lixi studies when compared to the IDeg Lira studies（4.0-5.0 mmol/L and 4.4-5.6 mmol/L）, and the IDeg Lira study used a greater average dose of insulin glargine when compared to the i Glar Lixi studies（66 U/d vs 40 U/d）.CONCLUSION Both i Glar Lixi and IDeg Lira effectively reduce glycated haemoglobin. Indirect comparisons, using insulin glargine as the common comparator, suggest that IDeg Lira reduces glycated haemoglobin to a greater extent than i Glar Lixi. However, given the limitations of indirect comparisons, robust head to head studies and real-world data would better inform clinician choice and clinical practice guidelines.